BL Infusion Trial:Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia

NCT05102162 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: IRB202101979 -AOCR41108
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The study plans to randomize a total of 240 patients infected with Gram-negative bacterial pneumonia to receive beta-lactam (meropenem, cefepime, or piperacillin/tazobactam) continuous or intermittent infusion and collect baseline and regular follow-up respiratory cultures to assess the development of new resistance. The investigators will measure beta-lactam concentration to assess the impact of drug exposure on the bacterial resistance.

Conditions

Pneumonia

Outcome Measures

Primary Outcomes (1)

• Gram-negative Bacterial Resistance Emergence Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens

  Bacterial resistance is defined as new numeric increases (\>/=2 fold) in the bacterial MIC during the follow-up period compared to the baseline when starting beta-lactam therapy. MICs were collected from respiratory samples and compared from study enrollment to end of the follow-up period for at least a 2 fold increase in MIC.

  4 weeks

Secondary Outcomes (9)

• Superinfection Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.

  4 weeks

• Microbiologic Eradication Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens

  4 weeks

• Clinical Cure at Day 7 of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens

  7 Days

• Clinical Cure at the End of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens

  4 weeks

• Mortality Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens

  4 weeks

Study Arms (2)

Continuous Antibiotic Dose Over 24 hours Arm

ACTIVE COMPARATOR

Subjects will be receiving a continuous dose of antibiotic prescribed by their doctor for the duration they choose.

Drug: Cefepime, Meropenem, or Piperacillin/Tazobactam

Intermittent Antibiotic Dose Over 30 minutes

ACTIVE COMPARATOR

Subjects will be receiving an intermittent dose of antibiotic prescribed by their doctor for the duration they choose.

Drug: Cefepime, Meropenem, or Piperacillin/Tazobactam

Interventions

Cefepime, Meropenem, or Piperacillin/Tazobactam DRUG

A 1:1 randomization scheme based on the infusion duration (continuous over 24 hours or intermittent over 30 minutes) with stratification based on the beta-lactam prescribed (cefepime, meropenem, or piperacillin/tazobactam)

Also known as: Maxipime, Merrem

Continuous Antibiotic Dose Over 24 hours Arm

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admission to the ICU with severe pneumonia (IDSA/ATS 2016/2019): presence of signs, symptoms and confirmatory chest imaging consistent with pneumonia (e.g. fever, cough and pulmonary infiltrate by chest radiograph)
• Age ≥18 years
• Positive respiratory culture (with or without an initial positive rapid identification test and/or Gram stain) for Gram-negative bacteria including, but not limited to, P. aeruginosa, K. pneumoniae, E. coli, S. marcescens, H. influenzae, Enterobacter spp., M. catarrhalis, A. baumannii, Achromobacter spp., P. mirabilis, and/or B. cepacia
• Received within the last 72 hours or will receive meropenem, cefepime, or piperacillin/tazobactam therapy

You may not qualify if:

• Pregnancy
• Prisoners
• Allergy to the beta-lactams to be administered in this study
• On renal replacement therapy at the time of randomization
• Baseline culture resistant to the beta-lactams in the study
• COVID patients enrolled in other trials

Sponsors & Collaborators

• University of Florida: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Pneumonia

Interventions

Cefepime; Meropenem; Piperacillin; Tazobactam

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; Ampicillin; Penicillin G; Penicillins; Penicillanic Acid; Sulfones

Limitations and Caveats

* Early termination leading to a small sample size and under-powered study. * Repeat positive cultures may have been due to colonization and not active infection, especially in participants demonstrating clinical cure prior to repeat cultures. * This study used MICs, which are generally accepted to have variability with repeat assessments, potentially up to 200% or more.

Results Point of Contact

• Title: Nicole Maranchick
• Organization: University of Florida College of Pharmacy

n.maranchick@cop.ufl.edu

352-273-6803

Study Officials

• Charles Peloquin

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2021
• First Posted: November 1, 2021
• Study Start: December 17, 2021
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: December 12, 2023
• Results First Posted: December 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)